Lesion Glycolysis Tumor Research Articles

An Investigation of the Relationship Between 18F-FDG PET/CT Parameters of Primary Tumors and Lymph Node Metastasis in Resectable Non-small Cell Lung Cancer.

Mediastinal lymph node metastasis is an important prognostic factor in non-small cell lung cancer (NSCLC) patients without distant metastases. 18F-2-fluoro-2-deoxy-Dglucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) is recommended for detecting and staging lymph nodes and distant metastases in NSCLC patients. This study aims to investigate whether maximum standardized uptake (SUVmax), mean standardized uptake (SUVmean), metabolic tumor volume (MTV), and tumor lesion glycolysis (TLG) values of the primary tumor measured by 18F-FDG PET/CT in resectable NSCLC can predict preoperative lymph node metastasis. This retrospective study included eighty NSCLC patients who underwent preoperative Positron Emission Tomography/Computed Tomography (PET/CT) for diagnosis and staging. The patients were stage I-III and had no distant metastases. Tumor metabolic parameters such as SUVmax, SUVmean, MTV, and TLG at PET/CT imaging were measured for preoperative diagnosis and staging, and the postoperative pathology results of the patients were examined. The pathology results divided patients with and without lymph node metastasis into two groups. The groups were compared with the student's t-test and chi-square test regarding 18F-FDG PET/CT tumor metabolic parameters and other parameters. Fifteen (18.8%) patients were female, and 65 (81.3%) were male. According to the postoperative pathology results, while 30 (37.5%) patients had lymph node metastasis, 50 (62.5%) did not. There was a significant difference between the groups regarding tumor SUVmax and SUVmean values (p = 0.036, p = 0.045). Overall survival in the N0 group was significantly higher than in the N1 + N2 group (p = 0.034); median survival was 30.2 months in N0 cases and 27.3 months in N1 and N2 groups. SUVmax and SUVmean values are significantly higher in patients with lymph node metastases than in patients without lymph node metastases, and this finding may provide useful information for predicting lymph node metastasis in patients with resectable NSCLC.

Prognostic role of quantitative [18F]FDG PET/CT parameters in adrenocortical carcinoma

PurposeWe aimed to evaluate the prognostic potential of baseline [18F]FDG PET/CT for overall survival (OS) in patients with adrenocortical carcinoma (ACC).MethodsWe performed a retrospective analysis of 67 treatment-naïve ACC patients with available [18F]FDG PET/CT at time of initial diagnosis. Pretherapeutic PETs of primary tumors were manually segmented and quantitative parameters (maximum/mean/peak standardized uptake value (SUVmax/mean/peak), metabolic tumor volume (MTV) and tumor lesion glycolysis (TLG, defined as TV*SUVmean) were derived. Based on a visual read, absence (M0) or presence of metastatic disease (M1) were evaluated. Kaplan–Meier and Cox regression analyses were used to determine the prognostic value of the above mentioned markers on overall survival adjusted for established prognostic markers.Results24/67 patients (36%) presented with M0 based on PET/CT, while the remaining 43/67 (64%) had M1-status. 32/67 patients died during follow-up and median OS was 48 months. In 12% of patients FDG-PET detected additional metastatic lesion not clearly visible by CT only. In univariable analysis, all quantitatively derived PET parameters failed to reach significance (P ≥ 0.1), and only PET/CT-based M1-status and Ki-67 were associated with increased mortality (M1: HR 13.89, 95% CI 4.15–86.32, P < 0.001; Ki-67 HR 1.29, 95% CI 1.16–1.42; P < 0.0001). Using multivariable Cox regression analyses, M1-status (HR 9.69, 95% CI 2.82–60.99) and Ki-67 index (HR 1.29, 95% CI 1.13–1.04; P < 0.05) remained significant associated with OS.ConclusionIn treatment-naïve ACC patients, the quantitative PET parameter failed to predict OS, but presence of metastases detected by [18F]FDG PET/CT and Ki-67 index were independently associated with shorter OS. Therefore, a simple visual PET-based read-out is of prognostic value at initial diagnosis, while time-consuming PET-based quantification can be omitted.

Low 18F-fluorodeoxyglucose dose positron emission tomography assisted by a deep-learning image-denoising technique in patients with lymphoma.

Patients with lymphoma receive multiple positron emission tomography/computed tomography (PET/CT) exams for monitoring of the therapeutic response. With PET imaging, a reduced level of injected fluorine-18 fluorodeoxyglucose ([18F]FDG) activity can be administered while maintaining the image quality. In this study, we investigated the efficacy of applying a deep learning (DL) denoising-technique on image quality and the quantification of metabolic parameters and Deauville score (DS) of a low [18F]FDG dose PET in patients with lymphoma. This study retrospectively enrolled 62 patients who underwent [18F]FDG PET scans. The low-dose (LD) data were simulated by taking a 50% duration of routine-dose (RD) PET list-mode data in the reconstruction, and a U-Net-based denoising neural network was applied to improve the images of LD PET. The visual image quality score (1 = undiagnostic, 5 = excellent) and DS were assessed in all patients by nuclear radiologists. The maximum, mean, and standard deviation (SD) of the standardized uptake value (SUV) in the liver and mediastinum were measured. In addition, lesions in some patients were segmented using a fixed threshold of 2.5, and their SUV, metabolic tumor volume (MTV), and tumor lesion glycolysis (TLG) were measured. The correlation coefficient and limits of agreement between the RD and LD group were analyzed. The visual image quality of the LD group was improved compared with the RD group. The DS was similar between the RD and LD group, and the negative (DS 1-3) and positive (DS 4-5) results remained unchanged. The correlation coefficients of SUV in the liver, mediastinum, and lesions were all >0.85. The mean differences of SUVmax and SUVmean between the RD and LD groups, respectively, were 0.22 [95% confidence interval (CI): -0.19 to 0.64] and 0.02 (95% CI: -0.17 to 0.20) in the liver, 0.13 (95% CI: -0.17 to 0.42) and 0.02 (95% CI: -0.12 to 0.16) in the mediastinum, and -0.75 (95% CI: -3.42 to 1.91), and -0.13 (95% CI: -0.57 to 0.31) in lesions. The mean differences in MTV and TLG were 0.85 (95% CI: -2.27 to 3.98) and 4.06 (95% CI: -20.53 to 28.64) between the RD and LD groups. The DL denoising technique enables accurate tumor assessment and quantification with LD [18F]FDG PET imaging in patients with lymphoma.

Predictive value of Dmax and %ΔSUVmax of 18F-FDG PET/CT for the prognosis of patients with diffuse large B-cell lymphoma

PurposeTo investigate the prognosis value of a combined model based on 18F-fluoro-deoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) baseline and interim parameters in patients with diffuse large B-cell lymphoma (DLBCL).MethodsWe retrospectively analyzed the PET metabolic parameters and clinical data of 154 DLBCL patients between December 2015 and October 2020. All of these patients underwent 18F-FDG PET/CT scan before treatment and after three or four courses of chemotherapy. The optimal cut-off values for quantitative variables were determined by the receiver operating characteristic (ROC) curve. The baseline and interim PET/CT parameters, which respectively included maximum standardized uptake value (SUVmax0), total metabolic tumor volume (TMTV0), standardized total metabolic tumor volume (STMTV0), and the distance between the two furthest lesions (Dmax) and total tumor lesion glycolysis (TTLG1), SUVmax1, TMTV1, and the rate of change of SUVmax (%ΔSUVmax), and clinical characteristics were analyzed by chi-squared test, Kaplan-Meier survival curve, and Cox regression analysis.ResultsOf 154 patients, 35 exhibited disease progression or recurrence. ROC analysis revealed that baseline 18F-FDG PET/CT metabolic parameters, including maximum standardized uptake value (SUVmax0), total metabolic tumor volume (TMTV0), standardized total metabolic tumor volume (STMTV0), and the distance between the two furthest lesions (Dmax), along with interim 18F-FDG PET/CT metabolic parameters such as total tumor lesion glycolysis (TTLG1), SUVmax1, TMTV1, and the rate of change of SUVmax (%ΔSUVmax), were predictive of relapse or progression in DLBCL patients (P < 0.05). The chi-squared test showed that TMTV0, STMTV0, Dmax, SUVmax1, TMTV1, TTLG1, %ΔSUVmax, Deauville score, IPI, Ann Arbor stage, and LDH were associated with patient prognosis (P < 0.05). Multivariate Cox regression analysis showed that Dmax (P = 0.021) and %ΔSUVmax (P = 0.030) were independent predictors of prognosis in DLBCL patients. There were statistically significant differences in PFS among the three groups with high, intermediate, and low risk according to the combination model (P < 0.001). The combination model presented higher predictive efficacy than single indicators.ConclusionThe combined model of baseline parameter Dmax and intermediate parameter %ΔSUVmax of 18F-FDG PET/CT improved the predictive efficacy of PFS and contributed to the risk stratification of patients, providing a reference for clinical individualization and precision treatment.

Lesion Analysis in PERCIST 1.0: Clinical Ease versus Research Requisite-Where Does the Balance Exist?

Background Semiqualitative parameter SUVmax has been the most frequently used semiquantitative positron emission tomography (PET) parameter for response evaluation, but only metabolic activity of a single (most metabolic) lesion is predicted. Newer response parameters such as tumor lesion glycolysis (TLG) incorporating lesions' metabolic volume or whole-body metabolic tumor burden (MTBwb) are being explored for response evaluation. Evaluation and comparison of response with different semiquantitative PET parameters such as SUVmax and TLG in most metabolic lesion, multiple lesions (max of five), and MTBwb in advanced non-small cell lung cancer (NSCLC) patients were made. The different PET parameters were analyzed for response evaluation, overall survival (OS), and progression-free survival (PFS). Methods 18 F-FDG-PET/CT (18-fluorine-fluorodeoxyglucose positron emission tomography/computed tomography) imaging was performed in 23 patients (M = 14, F = 9, mean age = 57.6 years) with stage IIIB-IV advanced NSCLC before initiation of therapy with oral estimated glomerular filtration rate-tyrosine kinase inhibitor for early and late response evaluation. The quantitative PET parameters such as SUVmax and TLG were measured in single (most metabolic) lesion, multiple lesions, and MTBwb. The parameters SUVmax, TLG, and MTBwb were compared for early and late response evaluation and analyzed for OS and PFS Results No significant difference in change in response evaluation was seen in patients evaluated with most metabolic lesion, multiple lesions, or MTBwb. Difference in early (DC 22, NDC 1) and late (DC 20, NDC 3) response evaluation was seen that remained unchanged when lesions were measured in terms of number of lesions or the MTBwb. The early imaging was seen to be statistically significant to the OS compared with late imaging. Conclusions Single (most metabolic) lesion shows similar disease response and OS to multiple lesions and MTBwb. Response evaluation by late imaging offered no significant advantage compared with early imaging. Thus, early response evaluation with SUVmax parameter offers a good balance between clinical ease and research requisition.

Repeatability of metabolic tumor burden and lesion glycolysis between clinical readers.

The Metabolic Tumor Volume (MTV) and Tumor Lesion Glycolysis (TLG) has been shown to be independent prognostic predictors for clinical outcome in Diffuse Large B-cell Lymphoma (DLBCL). However, definitions of these measurements have not been standardized, leading to many sources of variation, operator evaluation continues to be one major source. In this study, we propose a reader reproducibility study to evaluate computation of TMV (& TLG) metrics based on differences in lesion delineation. In the first approach, reader manually corrected regional boundaries after automated detection performed across the lesions in a body scan (Reader M using a manual process, or manual). The other reader used a semi-automated method of lesion identification, without any boundary modification (Reader A using a semi- automated process, or auto). Parameters for active lesion were kept the same, derived from standard uptake values (SUVs) over a 41% threshold. We systematically contrasted MTV & TLG differences between expert readers (Reader M & A). We find that MTVs computed by Readers M and A were both concordant between them (concordant correlation coefficient of 0.96) and independently prognostic with a P-value of 0.0001 and 0.0002 respectively for overall survival after treatment. Additionally, we find TLG for these reader approaches showed concordance (CCC of 0.96) and was prognostic for over -all survival (p ≤ 0.0001 for both). In conclusion, the semi-automated approach (Reader A) provides acceptable quantification & prognosis of tumor burden (MTV) and TLG in comparison to expert reader assisted measurement (Reader M) on PET/CT scans.

The potential application of MR-derived ADCmin values from 68Ga-DOTATATE and 18F-FDG dual tracer PET/MR as replacements for FDG PET in assessment of grade and stage of pancreatic neuroendocrine tumors

BackgroundTo evaluate the utility of 68Ga-DOTATATE and 18F-FDG PET/MR for prediction of grade and stage of pancreatic neuroendocrine tumors (PNETs), and to examine the correlation between parameters obtained from FDG PET and diffusion-weighted imaging (DWI) MR parameters.MethodsA retrospective study using 68Ga-DOTATATE and 18F-FDG PET/MR imaging was performed between April 2020 and May 2022 on 46 individuals with histologically confirmed PNETs. Metabolic tumor volume (MTV), maximum standardized uptake value (FSUVmax), and tumor lesion glycolysis (TLG) for FDG; somatostatin receptor density (SRD), maximum standardized uptake value (GSUVmax), and total lesion somatostatin receptor density (TLSRD) for DOTATATE; and minimum and mean apparent diffusion coefficient (ADCmin and ADCmean) values for MRI, respectively. We performed Spearman’s correlation analysis to examine the links between these variables and primary tumor stage and grading.ResultsHigher PNET grading was associated with higher FSUVmax, MTV, and TLG values (P < 0.05). TLG, SRD, ADCmin, and ADCmean values were correlated with N staging, while SRD, MTV, ADCmin, TLG, and ADCmean were associated with M staging. Notably, ADCmin was a negative correlation between FSUVmax (r = − 0.52; P < 0.001), MTV (r = − 0.50; P < 0.001), and TLG (r = − 0.56; P < 0.001).ConclusionsThis study highlights significant correlative relationships between FDG PET-derived parameters and ADCmin. ADCmin may offer utility as a tool for PNET staging and grading in lieu of FDG PET. 68Ga-DOTATATE PET/MR alone may be a sufficient alternative to dual tracer PET/MR when conducting grading and staging of primary PNETs.

Baseline volumetric parameters of PET/CT &lt;sup&gt;18&lt;/sup&gt;F-FDG and international prognostic index at patients with diffuse B-cell large cell lymphoma

INTRODUCTION: Metabolic tumor volume (MTV) and Tumor lesion glycolysis (TLG) are used in 18F-fluorodeoxyglucose Positron-Emission Tomography combined with Computed Tomography (18F-FDG PET/CT) as biometric markers in whole tumor. International prognostic index (IPI) has been used during 30 years at patients with diffuse B-cell large cell lymphoma (DLBCL) for prognosis, use MTV and TLG was unknown. Our aims were to determinate the best statistical relationship between MTV, TLG and IPI in patients with DLBCL.OBJECTIVE: Complex study of baseline volumetric parameters PET/CT with 18F-FDG at patients with DLBCL and assessment of their correlation with prognostic groups.MATERIALS AND METHODS: Baseline 18F-FDG PET/CT performed in 31 primary patients with DLBCL and evaluated SUVmax, MTV, TMTV, TLG, TTLG at different involved anatomic zones; correlation between PET biomarkers and prognostic groups of patients.Statistics: The research materials were subjected to statistical processing using the methods of correlation and regression analyses.RESULTS: SUVmax mean level didn’t discerned at patients of low and high-risk groups, but TMTV has been less in favorable prognostic, than in unfavorable groups (152±3.0 sm3 vs 890±178 sm3 p&lt;0,01); the same TTLG (1291±474 g/ml×sm3 vs 7640±2067 g/ml×sm3 , p&lt;0.01) and IMA (6.7±0.7 vs 9.2±0.6; p&lt;0,01). All volumetric parameters have been less at patients with supradiaphragmatic lymph nodes, than infradiaphragmatic lymph nodes and bones too. Significant positive correlation was found between the TMTV u TTLG (p=0.965; p&lt;0,001), between TMTV, TTLG and progressive disease risk (p=0.735; p=0.747; p&lt;0,001). The regression analysis was derived to estimate the connection PET biomarkers and progressive disease risk.DISCUSSION: The 30-year experience of using IPI in assessing the prognosis of patients with DLBCL has shown its insufficient effectiveness in many clinical situations, and the R-IPI prognostic model has been tested on a smaller number of patients and can only be considered additionally. We studied in detail the initial volumetric parameters of patients with DLBCL in different regions of the lesion and their relationship with the level of prognosis according to the IPI criteria. Our data on large values of volumetric parameters in the infradiaphragmatic areas and bones may be related to the worse prognosis in patients with these localizations. Further broader studies of the initial volumetric biomarkers of PET in DLBCL patients will contribute to the development of approximate boundaries of specific volumetric parameters for different tumor localizations.CONCLUSION: The results obtained showed that the baseline volumetric parameters PET/CT at patients with DLBCL have significant connection with prognostic groups of patients and can be additional factors to influence of tactics of therapy.

Whole body FDG PET/MR for progression free and overall survival prediction in patients with relapsed/refractory large B-cell lymphomas undergoing CAR T-cell therapy

BackgroundTo find semi-quantitative and quantitative Positron Emission Tomography/Magnetic Resonance (PET/MR) imaging metrics of both tumor and non-malignant lymphoid tissue (bone marrow and spleen) for Progression Free Survival (PFS) and Overall Survival (OS) prediction in patients with relapsed/refractory (r/r) large B-cell lymphoma (LBCL) undergoing Chimeric Antigen Receptor (CAR) T-cell therapy.MethodsA single-center prospective study of 16 r/r LBCL patients undergoing CD19-targeted CAR T-cell therapy. Whole body 18F-fluorodeoxyglucose (FDG) PET/MR imaging pre-therapy and 3 weeks post-therapy were followed by manual segmentation of tumors and lymphoid tissues. Semi-quantitative and quantitative metrics were extracted, and the metric-wise rate of change (Δ) between post-therapy and pre-therapy calculated. Tumor metrics included maximum Standardized Uptake Value (SUVmax), mean SUV (SUVmean), Metabolic Tumor Volume (MTV), Tumor Lesion Glycolysis (TLG), structural volume (V), total structural tumor burden (Vtotal) and mean Apparent Diffusion Coefficient (ADCmean). For lymphoid tissues, metrics extracted were SUVmean, mean Fat Fraction (FFmean) and ADCmean for bone marrow, and SUVmean, V and ADCmean for spleen. Univariate Cox regression analysis tested the relationship between extracted metrics and PFS and OS. Survival curves were produced using Kaplan–Meier analysis and compared using the log-rank test, with the median used for dichotomization. Uncorrected p-values < 0.05 were considered statistically significant. Correction for multiple comparisons was performed, with a False Discovery Rate (FDR) < 0.05 considered statistically significant.ResultsPre-therapy (p < 0.05, FDR < 0.05) and Δ (p < 0.05, FDR > 0.05) total tumor burden structural and metabolic metrics were associated with PFS and/or OS. According to Kaplan-Meier analysis, a longer PFS was reached for patients with pre-therapy MTV ≤ 39.5 ml, ΔMTV≤1.35 and ΔTLG≤1.35. ΔSUVmax was associated with PFS (p < 0.05, FDR > 0.05), while ΔADCmean was associated with both PFS and OS (p < 0.05, FDR > 0.05). ΔADCmean > 0.92 gave longer PFS and OS in the Kaplan-Meier analysis. Pre-therapy bone marrow SUVmean was associated with PFS (p < 0.05, FDR < 0.05) and OS (p < 0.05, FDR > 0.05). For bone marrow FDG uptake, patient stratification was possible pre-therapy (SUVmean ≤ 1.8).ConclusionsMTV, tumor ADCmean and FDG uptake in bone marrow unaffected by tumor infiltration are possible PET/MR parameters for prediction of PFS and OS in r/r LBCL treated with CAR T-cells.Trial registrationEudraCT 2016–004043-36.

Combination of 18F-FDG PET/CT and convex probe endobronchial ultrasound elastography for intrathoracic malignant and benign lymph nodes prediction.

BackgroundPositron emission tomography–computed tomography (PET/CT) and convex probe endobronchial ultrasound (CP-EBUS) elastography are important diagnostic methods in predicting intrathoracic lymph nodes (LNs) metastasis, but a joint analysis of the two examinations is still lacking. This study aimed to compare the diagnostic efficiency of the two methods and explore whether the combination can improve the diagnostic efficiency in differentiating intrathoracic benign LNs from malignant LNs.Materials and MethodsLNs examined by EBUS-guided transbronchial needle aspiration (EBUS-TBNA) and PET/CT from March 2018 to June 2019 in Shanghai Chest Hospital were retrospectively analyzed as the model group. Four PET/CT parameters, namely, maximal standardized uptake value mean standardized uptake value (SUVmean), SUVmean, metabolic tumor volume (MTV), and tumor lesion glycolysis (TLG); four quantitative elastography indicators (stiff area ratio, mean hue value, RGB, and mean gray value); and the elastography grading score of targeted LNs were analyzed. A prediction model was constructed subsequently and the dataset from July to November 2019 was used to validate the diagnostic capability of the model.ResultsA total of 154 LNs from 135 patients and 53 LNs from 47 patients were enrolled in the model and validation groups, respectively. Mean hue value and grading score were independent malignancy predictors of elastography, as well as SUVmax and TLG of PET/CT. In model and validation groups, the combination of PET/CT and elastography demonstrated sensitivity, specificity, positive and negative predictive values, and accuracy for malignant LNs diagnosis of 85.87%, 88.71%, 91.86%, 80.88%, and 87.01%, and 94.44%, 76.47%, 89.47%, 86.67%, and 88.68%, respectively. Moreover, elastography had better diagnostic accuracies than PET/CT in both model and validation groups (85.71% vs. 79.22%, 86.79% vs. 75.47%).ConclusionEBUS elastography demonstrated better efficiency than PET/CT and the combination of the two methods had the best diagnostic efficacy in differentiating intrathoracic benign from malignant LNs, which may be helpful for clinical application.

The prognostic effect of pretreatment 18F-FDG PET/CT metabolic parameters in locally advanced Esophageal Squamous Cell Carcinoma treated with definitive chemoradiotherapy

IntroductionIn this study, we aimed to examine the relation between pre-treatment 18F-FDG PET/CT metabolic parameters [(including the maximum standard uptake value (SUVmax), metabolic tumor volume (MTV), and tumor lesion glycolysis (TLG)] and treatment response and survival in locally-advanced Esophageal Squamous Cell Cancer (ESCC) treated with definitive chemoradiotherapy (dCRT). MethodsA total 76 patients with locally-advanced ESCC who received dCRT between June 2015 and December 2019 were included in this retrospective study. Patients were divided into two groups as complete response (CR) or non-complete response (Non-CR) according to response to treatment. AUC was obtained as 0.749 (p < 0.001) in the ROC curve drawn by MTV for the CR. The MTV value was ≤12 cm3, with 72.1% sensitivity and 73.0% specificity. ResultsOf the 76 patients, 38 (50%) were male and 38 (50%) were female. The median age was 62 (39–84) years. The treatment response in 35 (46%) patients was CR. MTV value was >12cm3 in 41(54%) patients. Median follow-up time was 14.5 months. In patients with MTV>12cm3, median progression-free survival(mPFS) and median overall survival(mOS) were 9 months and 11 months, respectively, whereas mPFS and OS could not be reached in those with MTV≤12 cm3 (p < 0.001 and p < 0.001, respectively). In patients with non-CR, mPFS and mOS were 8 months and 9 months, respectively, whereas mPFS and OS could not be reached in patients with CR (p < 0.001 and p < 0.001, respectively). In multivariate analysis, age (odds ratio [OR], 1.07), ECOG PS (OR, 11.1), and MTV (OR, 4.73) were found to be the factors affecting treatment response. ConclusionIn our study, treatment response and MTV were found to be the factors associated with survival in patients treated with dCRT, showing the pre-treatment MTV value as a predictor of treatment response.

Reproducibility of Standardized Uptake Values Including Volume Metrics Between TOF-PET-MR and TOF-PET-CT.

PurposeTo investigate the reproducibility of tracer uptake measurements, including volume metrics, such as metabolic tumor volume (MTV) and tumor lesion glycolysis (TLG) obtained by TOF-PET-CT and TOF-PET-MR.Materials and MethodsEighty consecutive patients with different oncologic diagnoses underwent TOF-PET-CT (Discovery 690; GE Healthcare) and TOF-PET-MR (SIGNA PET-MR; GE Healthcare) on the same day with single dose−18F-FDG injection. The scan order, PET-CT following or followed by PET-MR, was randomly assigned. A spherical volume of interest (VOI) of 30 mm was placed on the liver in accordance with the PERCIST criteria. For liver, the maximum and mean standard uptake value for body weight (SUV) and lean body mass (SUL) were obtained. For tumor delineation, VOI with a threshold of 40 and 50% of SUVmax was used (VOI40 and VOI50). The SUVmax, SUVmean, SUVpeak, MTV and TLG were calculated. The measurements were compared between the two scanners.ResultsIn total, 80 tumor lesions from 35 patients were evaluated. There was no statistical difference observed in liver regions, whereas in tumor lesions, SUVmax, SUV mean, and SUVpeak of PET-MR were significantly underestimated (p < 0.001) in both VOI40 and VOI50. Among volume metrics, there was no statistical difference observed except TLG on VOI50 (p = 0.03). Correlation between PET-CT and PET-MR of each metrics were calculated. There was a moderate correlation of the liver SUV and SUL metrics (r = 0.63–0.78). In tumor lesions, SUVmax and SUVmean had a stronger correlation with underestimation in PET-MR on VOI 40 (SUVmax and SUVmean; r = 0.92 and 0.91 with slope = 0.71 and 0.72, respectively). In the evaluation of MTV and TLG, the stronger correlations were observed both on VOI40 (MTV and TLG; r = 0.75 and 0.92) and VOI50 (MTV and TLG; r = 0.88 and 0.95) between PET-CT and PET-MR.ConclusionPET metrics on TOF-PET-MR showed a good correlation with that of TOF-PET-CT. SUVmax and SUVpeak of tumor lesions were underestimated by 16% on PET-MRI. MTV with % threshold can be regarded as identical volumetric markers for both TOF-PET-CT and TOF-PET-MR.

Clinical Perspectives for 18F-FDG PET Imaging in Pediatric Oncology: Μetabolic Tumor Volume and Radiomics.

Pediatric cancer, although rare, requires the most optimized treatment approach to obtain high survival rates and minimize serious long-term side effects in early adulthood. 18F-FDG PET/CT is most helpful and widely used in staging, recurrence detection, and response assessment in pediatric oncology. The well-known 18F-FDG PET metabolic indices of metabolic tumor volume (MTV) and tumor lesion glycolysis (TLG) have already revealed an independent significant prognostic value for survival in oncologic patients, although the corresponding cut-off values remain study-dependent and not validated for use in clinical practice. Advanced tumor “radiomic” analysis sheds new light into these indices. Numerous patterns of texture 18F-FDG uptake features can be extracted from segmented PET tumor images due to new powerful computational systems supporting complex “deep learning” algorithms. This high number of “quantitative” tumor imaging data, although not decrypted in their majority and once standardized for the different imaging systems and segmentation methods, could be used for the development of new “clinical” models for specific cancer types and, more interestingly, for specific age groups. In addition, data from novel techniques of tumor genome analysis could reveal new genes as biomarkers for prognosis and/or targeted therapies in childhood malignancies. Therefore, this ever-growing information of “radiogenomics”, in which the underlying tumor “genetic profile” could be expressed in the tumor-imaging signature of “radiomics”, possibly represents the next model for precision medicine in pediatric cancer management. This paper reviews 18F-FDG PET image segmentation methods as applied to pediatric sarcomas and lymphomas and summarizes reported findings on the values of metabolic and radiomic features in the assessment of these pediatric tumors.

The Potential Prognostic Value of Dual-Imaging PET Parameters Based on 18F-FDG and 18F-OC for Neuroendocrine Neoplasms.

Background To identify parameters based on dual-imaging 18F-AlF-NOTA-octreotide (18F-OC) and 18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) for predicting the prognosis of neuroendocrine neoplasms (NENs). Materials and Methods Sixty-six patients (age: mean ± standard deviation (SD): 51.8 ± 11.8 years) who underwent both 18F-OC and 18F-FDG PET/CT imaging were enrolled in our retrospective study. The following PET parameters were measured: the maximum standardized uptake value (SUVmax) and the volumetric parameters—18F-OC SSR-derived tumor volume (TV) and somatostatin receptor expression (SRE, TV multiplied by the mean standardized uptake value (SUVmean)) and the 18F-FDG-derived multiple tumor volume (MTV) and tumor lesion glycolysis (TLG). The NETPET grade based on dual-imaging PET images was assessed. Progression-free survival (PFS) was set as an endpoint. Univariate and multivariate survival analyses were performed for PET parameters and clinical tumor data. Results In the univariate survival analyses of clinical information, PFS was significantly associated with age (>45.5 vs ≤45.5, years, P < 0.034) and the presence of bone metastases (P = 0.04). Higher values for the 18F-FDG and 18F-OC volumetric parameters and the NETPET grade were adverse factors for PFS according to the dual-imaging PET parameters. In the multivariate survival analysis, the NETPET grade and SRE were predictors of PFS in NEN patients. Conclusion The NETPET grade is a potential noninvasive prognostic biomarker for NENs.

Methodological Aspects of Measuring Metabolic Tumor Volume in Patients with Diffuse B-Cell Large Cell Lymphoma by PET/CT with 18F-FDG

Introduction: Metabolic Tumor Volume (MTV) and Total Tumor Lesion Glycolysis (TLG) are used in 18F-fluorodeoxyglucose Positron-Emission Tomography combined with Computed Tomography (18F-FDG PET/CT) as functional markers, indicating tracer uptake in whole tumor. MTV and TLG are not yet engaged in clinical practice, because volume measurement accuracy depends on the selected measurement method, and optimal MTV and TLG segmentation is not established.Purpose: Assessment of accuracy of metabolic tumor volume measurement ways, using 18F-FDG PET/CT in patients with Diffuse Large B-Cell Lymphoma (DLBCL).Material and methods: Baseline 18F-FDG PET/CT performed in 21 patients with DLBCL. Tumor Volume (TV), measured on contrast enhanced CT (CTTV), considered as reference. While measuring MTV, we aimed to achieve a 1:1 ratio between CTTV and MTV. If anatomical and metabolic tumor contours matched, MTV was considered true (MTVtrue). Overall MTV and TLG measurements are 254. Tumor contouring, using relative thresholds, was made around Standardized Uptake Value (SUVmax) of tracer in tumor and intact liver.Results: On CT, the size of the lesions varied from 24 to 241 mm, M = 103.4±62.3, Me = 93 (48.5–155.5). In 15 (71.4 %) foci, hypodense areas of necrosis were determined. PET imaging revealed high tracer uptake in all foci of varying degrees of intensity. SUVmax values in tumors ranged from 5.8 to 30.5, Me = 20.4 (17.3–23.2). No significant correlation was found between the size of the foci and SUVmax (ρ = 0.17, p = 0.4744). The best accuracy in measuring MTV was observed when several thresholds were applied: VOIPERCIST, VOI2.5, VOIauto-contour, as well as VOI10 %, VOI15 % and VOI20 %. The optimal absolute threshold values were SUV values in the range from 2 to 3, and relative values in the range from 10 % to 20 % of the SUVmax in the tumor. MTV underestimation was more often determined using relative cut-off indices in the range of25–50 % and SUV thresholds ≥ 5.3.Conclusion: The results obtained showed that the use of a single threshold value for MTV segmentation in patients with DLBCL is not advisable. The choice of the MTV measurement method should be carried out individually for each lesion, taking into account its shape, size and structure, as well as the intensity and uniformity of tracer uptake in the tumor and adjacent anatomical structures.

Value of Primary Rectal Tumor PET/MRI in the Prediction of Synchronic Metastatic Disease.

To analyze the associations between positron emission tomography (PET)/magnetic resonance imaging (MRI) features for primary rectal tumors and metastases. Between November 2016 and April 2018, 101 patients with rectal adenocarcinoma were included in this prospective study (NCT02537340) for whole-body PET/MRI for baseline staging. Two readers analyzed the PET/MRI; they assessed the semiquantitative PET features of the primary tumor and the N- and M-stages. Another reader analyzed the MRI features for locoregional staging. The reference standard for confirming metastatic disease was biopsy or imaging follow-up. Non-parametric tests were used to compare the PET/MRI features of the participants with or without metastatic disease. Binary logistic regression was used to evaluate the associations between the primary tumor PET/MRI features and metastatic disease. A total of 101 consecutive participants (median age 62years; range: 33-87years) were included. Metastases were detected in 35.6% (36 of 101) of the participants. Among the PET/MRI features, higher tumor lesion glycolysis (352.95 vs 242.70; P = .46) and metabolic tumor volume (36.15 vs 26.20; P = .03) were more frequent in patients with than in those without metastases. Additionally, patients with metastases had a higher incidence of PET-positive (64% vs 32%; P = .009) and MRI-positive (56% vs 32%; P = .03) mesorectal lymph nodes, extramural vascular invasion (86% vs 49%; P > .001), and involvement of mesorectal fascia (64% vs 42%; P = .04); there were also differences between the mrT stages of these two groups (P = .008). No differences in the maximum standardized uptake values for the primary tumors in patients with and without metastases were observed (18.9 vs 19.1; P = .56). Multivariable logistic regression showed that extramural vascular invasion on MRI was the only significant predictor (adjusted odds ratio, 3.8 [95% CI: 1.1, 13.9]; P = .001). PET/MRI facilitated the identification of participants with a high risk of metastatic disease, though these findings were based mainly on MRI features.

Weakly supervised segmentation of tumor lesions in PET-CT hybrid imaging.

.Purpose: We introduce and evaluate deep learning methods for weakly supervised segmentation of tumor lesions in whole-body fluorodeoxyglucose-positron emission tomography (FDG-PET) based solely on binary global labels (“tumor” versus “no tumor”).Approach: We propose a three-step approach based on (i) a deep learning framework for image classification, (ii) subsequent generation of class activation maps (CAMs) using different CAM methods (CAM, GradCAM, GradCAM++, ScoreCAM), and (iii) final tumor segmentation based on the aforementioned CAMs. A VGG-based classification neural network was trained to distinguish between PET image slices with and without FDG-avid tumor lesions. Subsequently, the CAMs of this network were used to identify the tumor regions within images. This proposed framework was applied to FDG-PET/CT data of 453 oncological patients with available manually generated ground-truth segmentations. Quantitative segmentation performance was assessed for the different CAM approaches and compared with the manual ground truth segmentation and with supervised segmentation methods. In addition, further biomarkers (MTV and TLG) were extracted from the segmentation masks.Results: A weakly supervised segmentation of tumor lesions was feasible with satisfactory performance [best median Dice score 0.47, interquartile range (IQR) 0.35] compared with a fully supervised U-Net model (median Dice score 0.72, IQR 0.36) and a simple threshold based segmentation (Dice score 0.29, IQR 0.28). CAM, GradCAM++, and ScoreCAM yielded similar results. However, GradCAM led to inferior results (median Dice score: 0.12, IQR 0.21) and was likely to ignore multiple instances within a given slice. CAM, GradCAM++, and ScoreCAM yielded accurate estimates of metabolic tumor volume (MTV) and tumor lesion glycolysis. Again, worse results were observed for GradCAM.Conclusions: This work demonstrated the feasibility of weakly supervised segmentation of tumor lesions and accurate estimation of derived metrics such as MTV and tumor lesion glycolysis.

P24.09 Association Between Circulating EGFR Mutant Tumor DNA and Tumor Lesion Glycolysis in Patients with EGFR Mutated Metastatic Lung Adenocarcinoma

Monitoring the circulating tumor DNA (ctDNA) in EGFR-mutated metastatic lung adenocarcinoma (MLA) patients (pts) recently has been established as a reliable tool for therapy guidance. Tumor lesion glycolysis (TLG) measurement on an 18F-FDG-PET/CT scan gives information for tumor metabolic activity and tumor volumetric data at the same time point. We proposed that dynamic TLG assessment together with ctDNA measurement at time of response evaluation will give additional information about treatment choices.

Prognostic Value of Combing Primary Tumor and Nodal Glycolytic-Volumetric Parameters of 18F-FDG PET in Patients with Non-Small Cell Lung Cancer and Regional Lymph Node Metastasis.

We investigated whether the combination of primary tumor and nodal 18F-FDG PET parameters predict survival outcomes in patients with nodal metastatic non-small cell lung cancer (NSCLC) without distant metastasis. We retrospectively extracted pre-treatment 18F-FDG PET parameters from 89 nodal-positive NSCLC patients (stage IIB–IIIC). The Cox proportional hazard model was used to identify independent prognosticators of overall survival (OS) and progression-free survival (PFS). We devised survival stratification models based on the independent prognosticators and compared the model to the American Joint Committee on Cancer (AJCC) staging system using Harrell’s concordance index (c-index). Our results demonstrated that total TLG (the combination of primary tumor and nodal total lesion glycolysis) and age were independent risk factors for unfavorable OS (p < 0.001 and p = 0.001) and PFS (both p < 0.001), while the Eastern Cooperative Oncology Group scale independently predicted poor OS (p = 0.022). Our models based on the independent prognosticators outperformed the AJCC staging system (c-index = 0.732 versus 0.544 for OS and c-index = 0.672 versus 0.521 for PFS, both p < 0.001). Our results indicate that incorporating total TLG with clinical factors may refine risk stratification in nodal metastatic NSCLC patients and may facilitate tailored therapeutic strategies in this patient group.

18F]FDG PET/CT quantitative parameters for the prediction of histological response to induction chemotherapy and clinical outcome in patients with localised bone and soft-tissue Ewing sarcoma

The application of [18F]FDG PET/CT in predicting histologic response to induction chemotherapy in patients with Ewing sarcoma (EWS) has been proposed using the values of pre-post treatment SUVmax as a referral parameter, although with heterogeneous results. The aim of this retrospective study was to evaluate the diagnostic accuracy of [18F]FDG PET/CT volumetric parameters (metabolic tumour volume (MTV) and total lesion glycolysis (TLG)) as compared to SUVmax to predict response to chemotherapy and clinical outcome in patients with localised EWS of bone and soft-tissue. Twenty-eight patients with non-metastatic EWS of bone (n = 20) and soft tissues (n = 8) who underwent a [18F]FDG PET/CT scan before (PET1) and after induction chemotherapy (PET2) were enclosed in the analysis. Values of PET metrics (SUVmax, MTV, TLG) at diagnosis and after neoadjuvant chemotherapy as well as the percentage change between PET1 and PET2 (ΔSUV, ΔMTV and ΔTLG) were correlated to histological response and to progression-free survival (PFS). ΔTLG (cut-off: -60%) is the best predictor for histologic response with 100% sensitivity and 77.8% specificity. MTV1 > 33.4 cm3 and TLG1 > 112 were also associated with a favourable histologic response (sensitivity 80% and specificity 77.8% for both). On multivariate analysis, SUV2 (> 3.3) and ΔTLG (< -18%) were independent predictors of worse PFS. [18F]FDG PET/CT could accurately predict histologic response to neoadjuvant chemotherapy in patients with EWS, also showing a possible prognostic value for future disease relapse. • The variation of the PET parameter tumour lesion glycolysis (TLG) can predict the histologic response to induction chemotherapy (sensitivity 100%, specificity 77.8%), in patients with Ewing sarcoma. • The percentage variation of TLG and the value of the SUVmax at PET scan after chemotherapy show a prognostic role for future disease relapse. The combination of both the parameters identifies three prognostic classes of patients with low, intermediate and high risk of disease relapse.